PMID- 12520519
OWN - NLM
STAT- MEDLINE
DCOM- 20030725
LR  - 20220311
IS  - 0730-2312 (Print)
IS  - 0730-2312 (Linking)
VI  - 88
IP  - 2
DP  - 2003 Feb 1
TI  - Tolerogenic dendritic cells induced by vitamin D receptor ligands enhance 
      regulatory T cells inhibiting allograft rejection and autoimmune diseases.
PG  - 227-33
AB  - Dendritic cells (DCs) not only induce but also modulate T cell activation. 
      1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] induces DCs with a tolerogenic 
      phenotype, characterized by decreased expression of CD40, CD80, and CD86 
      costimulatory molecules, low IL-12 and enhanced IL-10 secretion. We have found 
      that a short treatment with 1,25(OH)(2)D(3) induces tolerance to fully mismatched 
      mouse islet allografts that is stable to challenge with donor-type spleen cells 
      and allows acceptance of donor-type vascularized heart grafts. This effect is 
      enhanced by co-administration of mycophenolate mofetil (MMF), a selective 
      inhibitor of T and B cell proliferation that has also effects similar to 
      1,25(OH)(2)D(3) on DCs. Graft acceptance is associated with an increased 
      percentage of CD4(+)CD25(+) regulatory cells in the spleen and in the draining 
      lymph node that can protect 100% of syngeneic recipients from islet allograft 
      rejection. CD4(+)CD25(+) cells, able to inhibit the T cell response to a 
      pancreatic autoantigen and to significantly delay disease transfer by pathogenic 
      CD4(+)CD25(-) cells, are also induced by treatment of adult nonobese diabetic 
      (NOD) mice with 1,25-dihydroxy-16,23Z-diene-26,27-hexafluoro-19-nor vitamin D(3) 
      (BXL-698). This treatment arrests progression of insulitis and Th1 cell 
      infiltration, and inhibits diabetes development at non-hypercalcemic doses. The 
      enhancement of CD4(+)CD25(+) regulatory T cells, able to mediate transplantation 
      tolerance and to arrest type 1 diabetes development by a short oral treatment 
      with VDR ligands, suggests possible clinical applications of this approach.
CI  - Copyright 2002 Wiley-Liss, Inc.
FAU - Adorini, Luciano
AU  - Adorini L
AD  - BioXell, SpA, 20132 Milano, Italy. luciano.adorini@bioxell.com
FAU - Penna, Giuseppe
AU  - Penna G
FAU - Giarratana, Nadia
AU  - Giarratana N
FAU - Uskokovic, Milan
AU  - Uskokovic M
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Ligands)
RN  - 0 (Receptors, Calcitriol)
RN  - 1406-16-2 (Vitamin D)
RN  - 66772-14-3 (1,25-dihydroxyvitamin D)
SB  - IM
MH  - Animals
MH  - Dendritic Cells/*immunology
MH  - Diabetes Mellitus, Type 1/drug therapy/*immunology/prevention & control
MH  - Graft Rejection/immunology
MH  - Humans
MH  - Immune Tolerance/*immunology
MH  - Ligands
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Receptors, Calcitriol/immunology/metabolism
MH  - T-Lymphocytes/*immunology
MH  - Transplantation, Homologous/immunology
MH  - Vitamin D/*analogs & derivatives/immunology/*metabolism/therapeutic use
RF  - 41
EDAT- 2003/01/10 04:00
MHDA- 2003/07/26 05:00
CRDT- 2003/01/10 04:00
PHST- 2003/01/10 04:00 [pubmed]
PHST- 2003/07/26 05:00 [medline]
PHST- 2003/01/10 04:00 [entrez]
AID - 10.1002/jcb.10340 [doi]
PST - ppublish
SO  - J Cell Biochem. 2003 Feb 1;88(2):227-33. doi: 10.1002/jcb.10340.